Empirical evidence for definitions of episode, remission, recovery, relapse and recurrence in depression: a systematic review
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Epidemiology and Psychiatric Sciences (2019), 28, 544–562. © Cambridge University Press 2018 ORIGINAL ARTICLE
doi:10.1017/S2045796018000227
Empirical evidence for definitions of episode,
remission, recovery, relapse and recurrence in
depression: a systematic review
P. L. de Zwart1*, B. F. Jeronimus1,2 and P. de Jonge1,2
1
University of Groningen, University Medical Center Groningen, Department of Psychiatry, Interdisciplinary Center Psychopathology and
Emotion Regulation (ICPE), Groningen, The Netherlands
2
University of Groningen, Faculty of Behavioural and Social Sciences, Department of Developmental Psychology, Groningen, The Netherlands
Aims. For the past quarter of a century, Frank et al.’s (1991) consensus-based definitions of major depressive disorder
(MDD) episode, remission, recovery, relapse and recurrence have been the paramount driving forces for consistency in
MDD research as well as in clinical practice. This study aims to review the evidence for the empirical validation of Frank
et al.’s proposed concept definitions and to discuss evidence-based modifications.
Methods. A literature search of Web of Science and PubMed from 1/1/1991 to 08/30/2017 identified all publications
which referenced Frank et al.’s request for definition validation. Publications with data relevant for validation were
included and checked for referencing other studies providing such data.
Results. A total of 56 studies involving 39 315 subjects were included, mainly presenting data to validate the severity and
duration thresholds for defining remission and recovery. Most studies indicated that the severity threshold for defining
remission should decrease. Additionally, specific duration thresholds to separate remission from recovery did not add
any predictive value to the notion that increased remission duration alleviates the risk of reoccurrence of depressive symp-
toms. Only limited data were available to validate the severity and duration criteria for defining a depressive episode.
Conclusions. Remission can best be defined as a less symptomatic state than previously assumed (Hamilton Rating
Scale for Depression, 17-item version (HAMD-17) 44 instead of 47), without applying a duration criterion.
Duration thresholds to separate remission from recovery are not meaningful. The minimal duration of depressive symp-
toms to define a depressive episode should be longer than 2 weeks, although further studies are required to recommend
an exact duration threshold. These results are relevant for researchers and clinicians aiming to use evidence-based
depression outcomes.
Received 1 November 2017; Accepted 23 April 2018; First published online 17 May 2018
Key words: Depression, evidence-based psychiatry, mood disorders unipolar, outcome studies, systematic reviews.
Introduction In 1991, the MacArthur Foundation Network on the
Psychobiology of Depression concluded that the ran-
Major depressive disorder (MDD) is a common, often
domness with which investigators referred to key
chronic and recurrent condition, marked by persistent
changes in clinical status of individuals with depres-
suffering and poor overall health and with deleterious
sion led to considerable confusion in the literature
effects on psychosocial, academic, vocational and fam-
(Prien et al. 1991). Subsequently, a task force was
ily functioning. MDD is one of the most prevalent
initiated to achieve consensus about the definition of
mental disorders and the leading cause of disability
key stages, change points and outcome definitions
worldwide (World Health Organization, 2017), with
for MDD among clinical investigators and practicing
lifetime prevalence estimates ranging from 7% to
clinicians. The resulting report by Frank et al. (1991)
21% (Kessler & Bromet, 2013).
defined conceptualisations of an MDD episode, remis-
sion, recovery, relapse and recurrence (see Fig. 1 and
supplementary Table) by a set of five parameters or
* Address for correspondence: Paul L. de Zwart, Department of thresholds: two severity scores (cut-offs for ‘asymp-
Psychiatry, Interdisciplinary Center Psychopathology and Emotion
tomatic’ and fully symptomatic ranges) and three
Regulation (ICPE), University of Groningen, University Medical
Center Groningen (UMCG), P.O. box 30.001, 9700RB Groningen, The
durations (minimal consecutive time durations in the
Netherlands. fully or a-symptomatic range before an episode, remis-
(Email: p.l.de.zwart@student.rug.nl) sion, or recovery can be declared).
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/
4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227Definitions in depression: a systematic review 545
Fig. 1. Time course of depressive symptomatology in a hypothetical patient, showing an MDD episode, remission, relapse,
recovery and recurrence. These stages are operationalised using two severity criteria (S1, S2), and three duration criteria (D, E, F).
S1: Severity threshold separating asymptomatic from partially symptomatic range; S2: Severity threshold separating partially
symptomatic range from fully symptomatic range; t1, Start of MDD episode; t2, Start of episode remission; t3, End of episode
remission; t4, Relapse of MDD episode; t5: Start of episode recovery and end of MDD episode; t6, Start of MDD recurrence.
Specific consensus-based recommendations for they have substantial predictive value for a future
these thresholds were provided in Frank et al.’s course. For example, treatment is indicated for those
(1991) report and revised in a follow-up report by experiencing an episode because they have a worse
Rush et al. (2006). Both reports explicitly requested prognosis than those who are experiencing symptoms
empirical validations of these now widely used that do not meet episode criteria. Therefore, the oper-
consensus-based definitions. Therefore, the present ationalisations of these concepts (i.e. the choice of
paper reviews the accumulated evidence over the severity and duration thresholds) should be chosen
past 27 years to validate the proposed conceptualisa- in such a way that they have optimal prognostic
tions and operationalisations and to provide sugges- significance.
tions for future avenues. In particular, it should be possible to distinguish
remission from recovery (and therefore relapse from
recurrence), which are different only in their duration,
Conceptual discussion
by a difference in prognosis. The hypothesis is that
Here we focus on conceptualisations of MDD episode, those in remission have not (yet) fully recovered
remission, recovery, relapse and recurrence by Frank from the latently present episode (i.e. they are still
et al. (1991, see supplementary Table), which are undergoing a healing process) and therefore have a
based exclusively on severity (number/intensity) and relatively high relapse rate compared with those who
duration of clinical symptoms, and each has its own recovered. Those who recovered have a low recurrence
rationale and clinical implications. An MDD episode rate that is no longer dependent on the time since their
means that illness is present and that treatment is indi- last episode and equal to the incidence rate of a risk
cated. When the state of remission (a relatively brief factor-comparable population who never experienced
period without clinically relevant symptoms during an episode. Similarly, in cancer research, ‘full remis-
or at the end of an episode) is reached, no intensified sion’ is defined as the period during which any sign
treatment regimen is required or justified. A recovery of the disease is lacking, but during which a patient
(a sustained period of absence of clinically relevant is particularly vulnerable for a relapse of the tumour
symptoms, i.e. a sustained remission) means that the since latent disease might still be present. When the
episode has ended and treatment can be discontinued remission is of sufficiently long duration, the patient
or aimed at preventing subsequent episodes. Relapse/ can be (retrospectively) considered to be recovered or
recurrence imply a return of symptoms during remis- ‘cured’ as the passing of even more time does not pro-
sion/recovery, respectively, and indicate a need for vide additional protection to disease recurrence, the
treatment intensification. The implicit distinction risk of which is similar to the incidence risk of a com-
between relapse and recurrence is that a relapse is parable healthy population.
thought to be a return of symptoms of an ongoing epi- Some of the clinical status concepts that are the sub-
sode that was symptomatically suppressed, whereas a ject of this review are also defined in the Diagnostic
recurrence represents an entirely new episode. and Statistical Manual of mental disorders (DSM-5;
Importantly, these concepts can only have the American Psychiatric Association, 2013) and the
ascribed interpretations and treatment implications if International Classification of Diseases (ICD-10;
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227546 P. L. de Zwart et al.
Table 1. Comparison DSM-5 and ICD-10 definitions for depression concepts
Minimal consecutive time duration: DSM-5 ICD-10
Episode D Symptomatic range 2 weeks 2 weeksa
Remission E Asymptomatic range 2 months Not explicitly definedb
Recovery F Asymptomatic range Not explicitly definedb Not explicitly definedb
Asymptomatic Range cut-off 42 symptoms to no more than ‘Free from any significant mood
a mild degree symptoms’, not specified further
Symptomatic Range cut-off 51 out of 2 core symptoms and 52 out of 3 core symptoms and
55 out of 9 total symptoms 54 out of 10 total symptoms
a
If the symptoms are particularly severe and of very rapid onset, it may be justified to make the diagnosis after less than 2 weeks.
b
Although the term ‘recovery’ is mentioned in the DSM-5 and ICD-10, it is not explicitly defined. ‘Relapse’ is not mentioned in
DSM-5 and ICD-10, whereas a recurrent episode is defined in DSM-5 as a return of symptoms during a remission (i.e. equivalent
to the concept of ‘relapse’ by Frank et al. (1991)) and in ICD-10 as a depressive episode separated from a previous episode by at
least 2 months free from any significant mood symptoms.
World Health Organization, 1993), as summarised in studies. The literature search was last updated on
Table 1. August 30, 2017.
Methods/literature search Results
This systematic review largely adhered to PRISMA The 1570 identified papers (supplementary eFigure)
guidelines (Moher et al. 2009). To review empirical evi- included 214 duplicates and 26 non-obtainable papers.
dence regarding the definitions proposed by Frank The study selection criteria (as outlined above)
et al. (1991), we searched both Web of Science and reduced the number to 117 papers and yielded 49 add-
Pubmed for studies that referenced them without itional records via reference checks. From these 166
imposing language restrictions (see supplementary papers, 110 were excluded based on the full-text
PRISMA flow diagram). Duplicates and non- assessment. Thus 56 studies covering 39 315 subjects
obtainable studies were excluded. Based on title and were included, and summarised in Tables 2–5.
abstract, studies were excluded that (i) did not focus
on individuals with MDD, (ii) were non-empirical,
Severity thresholds
(iii) were of study types not expected to be useful for
the purpose of this review (see online supplement), Frank et al. (1991) categorised the level of MDD symp-
or (iv) focused on the evaluation of some association tomatology in three clinical ranges: a fully symptomatic
or cause-effect relation between variables. range that can indicate the start of an episode, an
The remaining articles were scrutinised for data that asymptomatic range that can indicate the start of a full
could (in)validate at least one of Frank’s definitions. remission, and a partially symptomatic range in between.
Because severity related criteria were necessarily The ‘asymptomatic range’ is supposed to represent the
instrument-specific we focused on articles determining normal range consistent with the absence of disorder.
cut-offs on the HAMD-17 and the Montgomery- The term is a bit of a misnomer as this range includes
Åsberg Depression Rating Scale (MADRS), which are the presence of a minor level of symptomatology asso-
the most widely used instruments (Zimmerman et al. ciated with the ‘healthy’ (non-depressed) population,
2004a). Studies using different methodologies were in which the average HAMD-17 score is about 3.2
included (see results section). Criteria to define state (Zimmerman et al. 2004b); however, for consistency,
duration should be maximally predictive of remaining the term asymptomatic will be used throughout this
in that state (Frank et al. 1991). Therefore, we sought review.
studies that show the remission/recovery and relapse/ Two instrument-specific ‘thresholds’ need to be
recurrence of depressive episodes over time (via sur- defined on the HAMD-17 and MADRS (most widely
vival curves or equivalent). used as endpoints in clinical trials; Zimmerman et al.
Two authors (PLdZ, BFJ) extracted data inde- 2004a) to operationalise these three different levels of
pendently and resolved discrepancies through dis- symptomatology (see Fig. 1). Frank et al. (1991) defined
cussion and consensus. References of included HAMD-17 scores 515 to correspond to the fully symp-
articles were searched for additional relevant tomatic range while HAMD-17 47 would indicate the
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227Definitions in depression: a systematic review 547
asymptomatic range, the latter of which is roughly depression and patient’s own judgement regarding
equivalent to MADRS 410–11 (Zimmerman et al. their remission (Zimmerman et al. 2012a, b). Within
2004c). the group of remitters as defined by Frank et al.
Regarding the severity thresholds, the 32 studies (1991), a substantial heterogeneity was observed with
that provided data are summarised in Tables 2–4. respect to reported symptoms (Zimmerman et al.
2012c), psychosocial impairment (Zimmerman et al.
2004e, 2007) and a range of other relevant outcomes
Severity threshold for the asymptomatic range
(Zimmerman et al. 2012d) (see Table 3).
Studies focusing on the asymptomatic threshold could
be roughly divided into three groups, reflecting differ-
Severity threshold for the fully symptomatic range
ences in the used criteria for determining the ‘best’
threshold for the asymptomatic range. Only one study focusing on the fully symptomatic
The first group of studies selected the optimal threshold was obtained (see Table 2). By using the
threshold by maximising the correspondence to some CGI-S of 2 or 3 as the gold standard, Leucht et al.
gold standard (Hawley et al. 2002; Zimmerman et al. (2013) advise a HAMD-17 threshold of 57 or 514,
2004d, 2005; Bandelow et al. 2006; Ballesteros et al. respectively.
2007; Riedel et al. 2010; Romera et al. 2011; Leucht
et al. 2013; Sacchetti et al. 2015), most often the
Duration threshold for episode
Clinical Global Impression-Severity scale (CGI-S) or
some measure of functioning (see Table 2). The second Frank et al. (1991) categorised the symptomatic period
group of studies based on the optimal asymptomatic following any non-depressive state using a time
threshold on the mean scores or statistical upper limits boundary, separating the time period before the symp-
of the general population (Zimmerman et al. 2004a, b; toms were recognised as part of a depressive episode
see Table 3). These two groups mentioned a variety of from the time period afterwards. The underlying
optimal asymptomatic thresholds for the HAMD-17 assumption was that developing transient depressive
ranging from 42 (Zimmerman et al. 2005) to 410 symptoms is not necessarily pathological, as long as
(Zimmerman et al. 2004b) and for the MADRS 44 they do not culminate in a long-lasting depressive epi-
(Zimmerman et al. 2004a, 2004d) to 411 (Bandelow sode. Regarding the validation of this duration criter-
et al. 2006). ion, Frank et al. (1991) state that an episode should
The third and largest group of studies compared the be declared ‘when it is unlikely that the patient will spon-
prognosis of patients with different levels of depres- taneously recover in the next day or two’. Although rather
sive symptomatology, usually in terms of relapse/ arbitrary, the concept is clear: for the validation of this
recurrence risk (see Table 4). Based on this informa- duration criterion, data are necessary that shed light on
tion, a threshold can be chosen that best distinguishes the prognosis of those with recently started depressive
those with a favourable from those with a bad progno- symptomatology.
sis, argued by Zimmerman et al. (2004a) to be the best Such data was provided by four studies (see
method of validating a threshold. Most of these studies Table 5). The meta-analysis by Whiteford et al. (2013)
show that the presence of ‘subthreshold’ symptoms covering the rate of spontaneous remission in untreated
(often called residual symptoms if occurring after an depression showed that this rate decreases continuously
MDD episode) was associated with an enhanced risk over time. However, the amount of data in the range of
of a (recurrent) episode or relapse (Maier et al. 1997; short duration of follow-up is rather scarce and the
Riso et al. 1997; Judd et al. 1998, 2000, 2016; Van studied population (wait-list and primary care samples)
Londen et al. 1998; Fava et al. 1999; Kanai et al. 2003; is not representative of the general population with
Taylor et al. 2004; Nierenberg et al. 2010; Dunlop depressive symptoms.
et al. 2012; Kiosses & Alexopoulos, 2013; Peselow One study in the general population showed that
et al. 2015). One study (Romera et al. 2011) did not 25% of depressive episodes remitted after 4 weeks
find this increased risk. Often authors implicitly and 50% after 8–12 weeks, using a methodology in
argued for a lower threshold for remission that does which onset and end of depressive episodes were
not encompass this level of symptomatology. Some retrospectively assessed by asking the respondents
studies also showed that remission as defined by for their depressive symptomatology in the past
Frank et al. (1991), HAMD-17 47, is associated with (Eaton et al. 1997). The finding of a median duration
a better prognosis than not achieving this level of of 12 weeks was replicated in the NEMESIS study
remission (Paykel et al. 1995; Pintor et al. 2004). using a similar methodology, which also shows that
Saliently, some other noteworthy studies showed a the rate of recovery quickly diminishes after these 12
large discrepancy between Frank’s definition of weeks (Spijker et al. 2002).
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227https://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
548
P. L. de Zwart et al.
Table 2. Asymptomatic threshold (above) and fully symptomatic threshold (below): Comparisons with a gold standard
Size C Age (range & Scale to determine Gold standard for asymptomatic Advised or implicated cut-off
First author Year Sample, countrya (N) (%) M (S.D.) at T1) cut-off range/remission for asymptomatic range
Asymptomatic
Hawley et al. 2002 Patients, GB 684 N/A N/A MADRS CGI-S (using two different methods; MADRShttps://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Table 3. Asymptomatic threshold: Comparison with general population (above) or other comparison (below)
Pub Sample, Size C Age (range & M (S.D.) Scale to determine Criteria for selecting Advised or implicated cutoff for
First author year country (N) (%) at T1) cut-off optimal cutoff asymptomatic range
Comparison with general population
Zimmerman et al. 2004a 569 31 M = 34 (8) MADRSa Gen.pop. mean 44
Gen.pop. mean + 1 SD 410, or upper limit of normal values
Zimmerman et al. 2004b 1014 51 M = 40 (12) HAMDa Gen.pop. mean HAMD-17 44 (slightly higher than Gen.
pop. mean)
Gen.pop. mean + 1 SD HAMD-17 47
Gen.pop. mean + 2 SD HAMD-17 410
Other comparisons
Zimmerman et al. 2004e Patients, USA 117 62 M = 43 (13), R = 18-79
Zimmerman et al. 2007 Patients, USA 50 62 M = 43 (13), R = 18–73
Definitions in depression: a systematic review
Zimmerman et al. 2012a Patients, USA 140 68 M = 50 (13)
Zimmerman et al. 2012b Patients, USA 63 65 M = 48 (14)
Zimmerman et al. 2012c Patients, USA 140 68 M = 50 (13)
Zimmerman et al. 2012d Patients, USA 142 68 M = 49 (14)
Gen.pop., general population; HAMD, Hamilton Rating Scale for Depression (a.k.a. HRSD, HDRS); MADRS, Montgomery–Åsberg Depression Rating Scale; M, mean; min., minimal; N,
number of participants; N/A, not available; R, range; S.D., standard deviation; Sx, symptoms; T1, baseline. USA, United States of America.
a
Based on a review of 10 studies for the MADRS and a review of 27 studies for the HAMD.
549https://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Table 4. Asymptomatic threshold: comparison of prognosis
550
Pub Size C Age (range & M (S.D.) Definition for bad prognosis (e.g. relapse, Cut-off that distinguishes between good
P. L. de Zwart et al.
First author year Sample, countrya (N) (%) at T1) recurrence, episode) and bad prognosis
Paykel et al. 1995 Patients, GB 57 61 R = 18–65 RDC MDD 51 month HAMD-17 47
Maier et al. 1997 Gen.pop. & patients, DE 400 N/A N/A DSM-3-R MDD 12 and a < 50% decrease from HAMD-17 43
Ex T1 at 2 consecutive visits or at the
last visit before discontinuation.
Kiosses & Alexopoulos 2013 Patients, USA 152 60 M = 72 (7), R = 60–89 PSR score 55b LIFE-PSR 42b
Peselow et al. 2015 Patients, USA 387 59 M= 32 (12), R = 16–77 Not clearly indicated; MADRS 515 or MADRS 48
meeting DSM-4 criteria for MDD.
Judd et al. 2016 Patients, USA 322 60 M = 40 (15), R = 17–76 PSR-MDD = 5/6 or PSR = 3b for 52 week PSR = 1b
DSM, Diagnostic and Statistical Manual; Ex., Episode; Gen.pop., General population; HAMD, Hamilton Rating Scale for Depression (a.k.a. HRSD, HDRS); LIFE-PSR, Longitudinal
Follow-up Examination (LIFE) Psychiatric Status Rating Scale (PSR); MADRS, Montgomery–Åsberg Depression Rating Scale; M, mean; min., minimal; N, number of participants; N/A,
not available; R, range; PSR, Psychiatric Status Ratings**; RDC, Research Diagnostic Criteria; S.D., standard deviation; Sx, symptoms; T1, baseline; QIDS-SR16, Quick Inventory of
Depressive Symptomatology 16-item self-rating scale.
a
Country codes (ISO Alpha-2 and 3): DE, Germany; ES, Spain; GB, United Kingdom; IT, Italy; JP, Japan; USA, United States of America.
b
Psychiatric status ratings: (1) asymptomatic (return to usual self); (2) residual/mild affective Sx; (3) partial remission, moderate Sx or impairment; (4) marked/major Sx or impairment; (5)
meets definite MDD criteria without prominent psychotic Sx or extreme impairment; (6) meets definite criteria with prominent psychotic Sx or extreme impairment.
c
The authors state that relapse becomes less likely when the MADRS score is lower, but there is no single cut-off that has high sensitivity and specificity for predicting relapse: ‘This suggests
that there is no particular cut-off that is sufficient to consider as ‘low enough’ to protect against future relapse, so the primary conclusion would be to strive for the lowest score possible’.
d
No particular cut-off: those with a greater number of residual symptom domains (out of nine possible DSM-IV criterion symptom domains) had a greater probability of relapse.https://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Table 5. Definitions of duration thresholds for episode, remission and recovery of major depressive disorder
Estimated
Sample, C Age (range & point of
First author Year country codea Size (N) (%) M (S.D.) at T1) rarity Episode Remission Recovery Relapse Recurrence
Duration thresholds for episode
Eaton et al. 1997 Gen.pop., USA 71 75 R = 18–70 Sadness/anhedonia N/A ≥1 year without N/A First Ex after recovery
& 2 other Sx depressive Ex
Spijker et al. 2002 Gen. pop., NL 250 67 R = 18–64 DSM-3-R def. via No/min. depressive No distinction N/A N/A
CIDI Sx on LCI for provided between
3 month (US remission and
NIMH def. +1 recovery
month)
Wakefield & 2013 Patients, USA 88 73 R = 18–98, ≥2 week sadness & Ex before T1, but N/A N/A Remitted at T1, but Ex
Schmitz M = 37 ≥4 Sx of adequate not at T1 T1–T2.
severity interview
Whiteford 2013 Patients, USA 749 73 M = 34 Differs per study Differs per study N/A N/A N/A
et al.
Duration thresholds for remission and recovery
Maj et al. 1992 Patients, IT 72 58 M = 42 (7), RDC after N/A ≥8 week absence of N/A MDD Ex after
R = 27–55 interview with prominent recovery
Definitions in depression: a systematic review
SADS-L dysphonic mood
(RDC MDD crit.
A) and presence
≤2 Sx MDD crit. B
(each HAMD ≤1)
Shea et al. 1992 Patients, USA 78 N/A R = 21–60 N/A RDC for MDD Ex N/A Stable MDD Sx 2 week of meeting No distinction
remission, RDC for MDD (PSR provided between
requiring ≥5b) after recovery relapse and
LIFE-II-PSRs ≤2b recurrence.
(min./no Sx) ≥8
week following
treatment
Paykel et al. 1995 Patients, USA 57 61 N/A ±10 month RDC MDD Dx 2 month Sx below N/A Return to RDC N/A
MDD criteria MDD ≥ 1 month
(retrosp. ass.) (retrosp. ass.)
Continued
551https://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Table 5. Continued
552
Estimated
P. L. de Zwart et al.
Sample, C Age (range & point of
First author Year country codea Size (N) (%) M (S.D.) at T1) rarity Episode Remission Recovery Relapse Recurrence
Eaton et al. 1997 Gen.pop., USA 80 62 R > 18 LCI MDD Ex [1], N/A 1 yearr in which N/A First Ex after recovery
i.e., sadness/ there was no
anhedonia & ≥2 MDD Ex
other Sx
Emslie et al. 1997 Patients, USA 59 46 M = 13 (3), ≥14 days MDD ≥14 days MDD MDD K-LIFE rating Ex MDD after Ex MDD after
R = 7–17 K-LIFE rating ≥5 K-LIFE rating ≥1 ≥1 ≥60 days remission recovery
Flint & Rifat 1997 Patients, CA 84 64 M = 74, DSM-3-R criteria Point of response Not explicitly def., DSM-3-R MDD criteria Same as relapse but
R = 60–80 for non-bipolar, (HAMD ≤10) but deducible. ≥1 week & HAMD ≥16 week of
non-psychotic followed by ≥16 within 16 week remission without
MDD & HAMD ≥2 week of after MDD relapse
≥16 HAMD ≤10 remission
Riso et al. 1997 Patients, USA 90 56 M = 38 (9.7) ±3 month Not def., but 3 week HAMD ≤6 ≥6 month HAMD ≤6 ≥2 week after a 2 week HAMD
inclusion RDC & response HAMD≥ ≥14 after 6 month
HAMD ≥14 14 [2] of recovery
Judd et al 1998 Patients, USA 237 63 M = 40 (15) ±29–37 RDC: >2 week No def. Period RDC >8 week MDD >2 week MDD PSR 5 >2 week MDD PSR 5
month PSR-MDD 5 or 6b PSR-MDD 1–2b PSR = 1b or 6b (RDC def.) or 6b (RDC def.)
before recovery (asymptomatic
recovery) or 2b
(residual
recovery)
Kessing et al. 1998 Patients, DK 17447 66 56 Period of When discharged >8 week after being Readmission to Readmission to
hospitalisation, from hospital. discharged from hospital ≤8 week hospital >8 week
ending when Remission ends the hospital after discharge after discharge
not readmitted ≥8 week, when (within remission (within recovery
8 week after recovery starts. period) period)
discharge
Van Londen 1998 Patients, NL 49 59 45 ±4 month DSM-3-R criteria 2 month Sx below Full remission ≥ 6 ≥1 month return to Recurrence defined as
et al. for MDD DSM-3-R MDD month MDD DSM-3-R, relapse, but during
threshold before recovery recovery.
(MADRShttps://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Van Weel- 1998 Patients, NL 222 61 R = 0–80 Day first MDD Dx No def., Ex ends as N/A N/A New code or Sx
Baumgarten end MDD in description ≥3
et al. case record, or month without
3 month such Sx
without Sx
Mueller et al. 1999 Patients, USA 380 61 M = 38 No explicit def. N/A The first of 8 wk of N/A No explicit def. String
no/min. Sx of MDD PSR
(defined as PSR= 1 ratings used for
or 2). Before course estimate
recovery PSR =
1–6
O’Leary et al. 2000 Patients, IE 85 57 M = 41 ICD-10 def. for Ex ≥2 week HAM-D No focus on recovery 2 week re-appearance N/A
or recurrenthttps://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
Table 5. Continued
554
Estimated
P. L. de Zwart et al.
Sample, C Age (range & point of
First author Year country codea Size (N) (%) M (S.D.) at T1) rarity Episode Remission Recovery Relapse Recurrence
Pintor et al. 2004 Patients, ES 138 68 M = 53 (16), Frank’s criteria Frank’s criteria N/A Frank’s criteria applied N/A
R≥18 applied using the applied using using the HDRS
HDRS the HDRS
Mattisson 2007 Patients, SE 344 68 R = 20–83 Retrospective No explicit def. No explicit def. No explicit def. No explicit def. Ex
et al. report on Ex, after an earlier Ex
with medium with a ‘well period’
degree of in-between. [4]
impairment
required.
Naz et al. 2007 Patients, USA 87 59 M = 31 ±14 month DSM-4 Dx by a ≥8 week N/A DSM-4 Ex after N/A
team of asymptomatic achieving remission.
psychiatrists, (only min. Sx). Partial relapse >min.
using all Partial Sx but not fulfilling
available remission: some criteria Ex.
information persistent Sx but
(e.g., SCID). not meeting
MDD criteria.
Cut-offs unclear.
Holma et al. 2008 Patients, FI 163 78 M = 42 ±18 month DSM-4 criteria for ≥2 month without N/A 2 week return to Return to Ex MDD
MDD based on fulfilling DSM-4 DSM-4 MDD within after ≥2 month of
interviews using MDD criteria. 2 month after being partial/full
graphic life Full remission below threshold remission
charts. when none of the
9 core Sx was
rated. Partial
remission ≤4 Sx.
Yiend et al. 2009 Patients, GB 37 81 M = 35 (12) DSM and RDC DSM and RDC ≥3 month with a PSR No distinction No distinction
criteria, but test criteria, but test of 1 or 2b between relapse and between relapse
remains unclear. remains unclear. recurrence and recurrence
De Jonge et al. 2010 Patients, NL 267 64 M = 43 (11) ±9 month DSM-4 criteria No distinction Defined as any No distinction Ex during recovery
using CIDI between period between between relapse and
remission and MDD Ex recurrence
recoveryhttps://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
O’Leary et al. 2010 Patients, IE 86 52 M = 38 ±2 month DSM-4 MDD 2 week HAM-D 12 and
R = 18–65 based on 2https://doi.org/10.1017/S2045796018000227
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
556
P. L. de Zwart et al.
Table 5. Continued
Estimated
Sample, C Age (range & point of
First author Year country codea Size (N) (%) M (S.D.) at T1) rarity Episode Remission Recovery Relapse Recurrence
Judd et al. 2016 Patients, USA 322 60 M = 40 (15), RDC criteria ≥2 Various def. of Both relapse and Both relapse and
R = 17–76 week with ≥5 Sx recovery were recurrence def. as recurrence def. as
including intense compared, first of 2 week with first of 2 week with
sadness or differing on syndromal MDD Sx syndromal MDD Sx
dysphoria severity (PSR = 1 (PSR = 5 or 6)b or (PSR = 5 or 6) or
vs. 2)b and minor depression minor depression
duration (4 or (PSR = 3)b. (PSR = 3)b.
8 week) [6]
ass., assessment; DSM, Diagnostic and Statistical Manual; CIDI, Composite International Diagnostic Interview; Dx, diagnosis; def., definition; Ex., Episode; Gen.pop., General population;
HAMD, Hamilton Rating Scale for Depression; LCI, Life chart interview; M, mean; MDD, Major Depressive Disorder or unipolar depression; min., minimal; N, number of participants; N/A,
not available; NIMH, National Institute of Mental Health; PSR, Psychiatric Status Ratingsb; R, range; RDC, Research Diagnosis Criteria; retr., retrospectively; SADS-L, Schedule for Affective
Disorders and Schizophrenia-Lifetime interview; S.D., standard deviation; Sx, symptoms; T1, baseline wave; T2, follow-up wave.
a
Country codes (ISO Alpha-2 and 3): CA, Canada; DE, Germany; DK, Denmark; ES, Spain; FI, Finland; GB, United Kingdom; IE, Ireland; IT, Italy; JP, Japan; MX, Mexico; NL, Netherlands;
SE, Sweden; USA, United States of America.
b
Psychiatric status ratings: (1) asymptomatic (return to usual self); (2) residual/mild affective Sx; (3) partial remission, moderate Sx or impairment; (4) marked/major Sx or impairment; (5)
meets definite MDD criteria without prominent psychotic Sx or extreme impairment; (6) meets definite criteria with prominent psychotic Sx or extreme impairment.
(1) Respondents rated whether they experienced ‘a time when you felt sad or blue and had some of these other problems (e.g., weight loss or sleeplessness)’.
(2) Response was defined in various ways, and each definition was tested for validity.
(3) Authors appear to mix up recurrence and relapse, but we denote time after patient recovered as recurrence.
(4) Medication use was seen as indication for not being healthy, thus these people were not at risk for recurrence.
(5) PSR ≥3 during some of these weeks count as residual Sx after remission, i.e., the patient is not yet considered to be relapsed or recurred before PSR ≥5.
(6) The authors suggest that 8 week duration was the standard before their paper was published, mistakenly, see Rush et al. (2006).Definitions in depression: a systematic review 557
Wakefield & Schmitz (2013) argued that ‘uncompli- Alexopoulos, 2013). However, the exact amount of
cated’ depressive episodes, defined as558 P. L. de Zwart et al.
However, even though none of these studies systemat- as this seems to be the definition that least ‘needs’
ically studied and compared the predictive value of all empirical validation; this can be understood as a rather
possible thresholds, we hypothesise that this is a gen- subjective clinical decision regarding the minimal level
eral finding that can be obtained irrespective of the of symptomatology that can be considered to be a dis-
chosen threshold, as a lower score on a depressive order. Therefore, there is not enough evidence to make
symptom scale increases the ‘symptomatic distance’ any recommendations regarding this threshold.
to the fully symptomatic threshold and therefore the
average time required for reaching that state. Indeed,
Duration threshold for episode
some studies show that the currently often-used
threshold (HAMD-17 47; Frank et al. 1991) also differ- Only a limited amount of studies showed data on the
entiates in this regard (Paykel et al. 1995; Pintor et al. prognosis of those with ‘recent-onset’ depression (see
2004). Studies using other methodologies for determin- Table 5). This can be explained by epidemiological
ing the best asymptomatic threshold – such as optimis- investigations that typically include depressed popula-
ing correspondence to clinical impressions of clinicians tions, for which it is unclear how long the depressive
(using the CGI-S as a gold standard), different func- symptoms have been present at the start of the studies.
tioning scales, or the general population – yield differ- Although two studies show that half of the depressive
ent optimal thresholds. The consensus among these episodes in the general population remit within 3
authors seems to be that the currently often-used months after their onset (Eaton et al. 1997; Spijker
threshold of HAMD-17 47 is too high, as it leads to et al. 2002), it seems likely that many short ‘episodes’
the inclusion of too many patients with poor function- of only a few days are missed since these episodes
ing (Sacchetti et al. 2015), who are psychosocially are infrequently retrospectively indicated, and short
impaired (Zimmerman et al. 2007) and who do not episodes are more easily forgotten than long ones
consider themselves as remitted (Zimmerman et al. (Moffitt et al. 2010). Therefore, the rate of early remis-
2012a). sion is probably even higher than suggested by these
Ultimately, the particular choice of asymptomatic studies.
threshold is rather arbitrary given the available evi- In general, the reviewed data suggest that the rate of
dence. Nonetheless, the currently often-used threshold (spontaneous) remission of depressive symptoms is
seems to be too high. We, therefore, suggest lowering relatively high when the onset of these symptoms is
the asymptomatic threshold to 44 on the HAMD-17; recent, especially during the first 12 weeks, but
this is on the low side of the suggested values in the diminishes quickly thereafter. This provides some jus-
obtained studies – which we think is justified given tification for the suggestion by Frank et al. (1991) of
the better functioning below this score (Sacchetti et al. requiring a certain amount of time at the fully symp-
2015) – although still above the mean score in the gen- tomatic level before defining a depressive episode.
eral population (Zimmerman et al. 2004b). It has been However, the currently required ‘waiting time’ of
shown that some patients who scored 47 on the only 2 weeks (see Table 1; DSM-5 criteria, APA,
HAMD-17 still met diagnostic criteria for MDD 2013; ICD-10 criteria, WHO, 1993) does not seem to
(Zimmerman et al. 2004e), which is another argument be based on empirical evidence. The reviewed studies
for our suggestion to lower the asymptomatic thresh- suggest that a longer time period might be advisable.
old to 44, as this largely prevents ‘remitted’ people Nonetheless, we refrain from a definitive conclusion,
from meeting the diagnostic criteria for MDD. This for which a prospective study in which the general
new HAMD-17 threshold is roughly equivalent to a population is screened with a high frequency (e.g.
threshold of 45 on the MADRS (Mittmann et al. weekly) for depressive symptomatology is required
1997), which is plausible given the reviewed evidence. but hitherto unavailable.
Note that these thresholds are useful as endpoints in
clinical studies, but do not necessarily mean that scor-
Duration thresholds for remission and recovery
ing below these thresholds should be the main treat-
ment goal for clinicians, as treating individual A substantial body of literature studying depressive
patients by striving for the lowest score possible still relapse/recurrence risk over time has been obtained
improves prognosis (Taylor et al. 2004). (see Table 5), but comparing the studies is not straight-
forward; the studies differed in their studied popula-
tions, their operationalisations of remission, recovery,
Severity threshold for the fully symptomatic range
relapse and recurrence, and in the involved treatments.
Only one study was obtained that provides some evi- Some studies were consistent with the idea of a ‘point
dence for the fully symptomatic cut-off (Leucht et al. of rarity’ (Frank et al. 1991) at which the relapse/recur-
2013). This relative lack of evidence is understandable, rence risk suddenly drops or becomes stable.
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227Definitions in depression: a systematic review 559
However, there is no consistency in the estimation of can best be defined as a less symptomatic state than
this time point. Combined with the fact that the major- assumed earlier (HAMD-17 44 instead of 47), with-
ity of studies do not show such a point of rarity, the out applying a duration criterion. Specific duration
most likely conclusion is that prognosis gradually thresholds to separate remission from recovery are
improves as remission/recovery duration is longer, not meaningful. Evidence suggests that the minimal
rather than suddenly at a particular point in time. duration of depressive symptoms before a depressive
The reviewed data do not suggest that any specific episode can be defined should be longer than 2
duration threshold to distinguish remission from recov- weeks, although further studies are required to recom-
ery is warranted to add predictive value to the observa- mend an exact duration threshold.
tion that prognosis improves over time as the duration
of the asymptomatic period increases. Not only were
the specific operationalisations of the duration criteria Supplementary material
by Frank et al. (1991) and Rush et al. (2006) not empiric-
The supplementary material for this article can be
ally supported, it seems that the whole concept of these
found at https://doi.org/10.1017/S2045796018000227
duration criteria must be rejected. The idea that a
reoccurrence of depressive symptoms shortly after
their initial remission constitutes a ‘relapse’ of the previ- Acknowledgements
ous episode, whereas their later reoccurrence is the first
sign of an entirely new episode, is a model that lacks We thank the editor and reviewers for their comments.
empirical support. Additionally, it is of no additional
value to the patient or clinician as the assumed origin
of the reoccurring symptoms has no implications for Conflict of interest
treatment or prognosis. None.
Thus, based on these results, the duration criteria for
declaring remission and recovery seem unnecessary.
We suggest that depressive remission can simply be Ethical standards
defined as the asymptomatic state after a depressive
episode, without applying any duration criterion. None applicable.
Stability of remission is then relatively low on the
first day but increases gradually with its duration.
Availability of data and materials
The term recovery can then be used as a concept that
includes more than just absence of symptoms, such The data regarding the process of screening and selec-
as social functioning or subjective well-being, possibly tion of the articles included in this systematic review
including the absence of significant treatment as this (after removal of identical articles) are available in an
would better fit the concept of recovery from a online supplement.
patient’s perspective.
Limitations References
American Psychiatric Association (2013). Diagnostic and
Limitations of this review include the greatly varying
Statistical Manual of Mental Disorders (DSM-5®). American
study populations and treatments within the included
Psychiatric Pub.: Washington, DC.
studies (which is also a strength). Moreover, a substan- Ballesteros J, Bobes J, Bulbena A, Luque A, Dal-Ré R, Ibarra
tial part of the data had to be extracted from survival N, Güemes I (2007). Sensitivity to change, discriminative
curves that only rarely showed confidence intervals performance, and cutoff criteria to define remission for
and often did not possess a clearly labelled time axis, embedded short scales of the Hamilton depression rating
making it difficult to assess exactly when the measure- scale (HAMD). Journal of Affective Disorders 102(1), 93–99.
ment began. Bandelow B, Baldwin DS, Dolberg OT, Andersen HF, Stein
DJ (2006). What is the threshold for symptomatic response
and remission for major depressive disorder, panic
Conclusions disorder, social anxiety disorder, and generalized anxiety
disorder? The Journal of Clinical Psychiatry 67(9), 1428–1434.
More than a quarter-century after the landmark paper Birmaher B, Williamson DE, Dahl RE, Axelson DA,
in which Frank et al. (1991) provided their consensus- Kaufman J, Dorn LD, Ryan ND (2004). Clinical
based definitions for depressive states (episode, remis- presentation and course of depression in youth: does onset
sion, recovery, relapse, recurrence), we reviewed the in childhood differ from onset in adolescence? Journal of the
empirical evidence. The data suggest that remission American Academy of Child Psychiatry 43(1), 63–70.
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227560 P. L. de Zwart et al.
de Jonge P, Conradi HJ, Kaptein KI, Bockting CLH, Korf J, recurrence after recovery from major depressive episodes
Ormel J (2010). Duration of subsequent episodes and and its predictors. Psychological Medicine 33(5), 839–845.
periods of recovery in recurrent major depression. Journal of Kennedy N, Abbott R, Paykel ES (2003). Remission and
Affective Disorders 125(1), 141–145. recurrence of depression in the maintenance era: long-term
Dunlop BW, Holland P, Bao W, Ninan PT, Keller MB (2012). outcome in a Cambridge cohort. Psychological Medicine 33
Recovery and subsequent recurrence in patients with (5), 827–838.
recurrent major depressive disorder. Journal of Psychiatric Kessing LV, Andersen PK, Mortensen PB, Bolwig TG
Research 46(6), 708–715. (1998). Recurrence in affective disorder: I – case register
Eaton WW, Anthony JC, Gallo J, Cai G, Tien A, Romanoski study. The British Journal of Psychiatry 172(1), 23–28.
A, Lyketsos C, Chen L-S (1997). Natural history of Kessler RC, Bromet EJ (2013). The epidemiology of
diagnostic interview schedule/DSM-IV major depression: depression across cultures. Annual Review of Public Health
the Baltimore epidemiologic catchment area follow-up. A. 34, 119–138.
M.A. Archives of General Psychiatry 54(11), 993–999. Kiosses DN, Alexopoulos GS (2013). The prognostic
Emslie GJ, Rush AJ, Weinberg WA, Gullion CM, significance of subsyndromal symptoms emerging after
Rintelmann J, Hughes CW (1997). Recurrence of major remission of late-life depression. Psychological Medicine 43
depressive disorder in hospitalized children and (2), 341–350.
adolescents. Journal of the American Academy of Child and Leucht S, Fennema H, Engel R, Kaspers-Janssen M, Lepping
Adolescent Psychiatry 36(6), 785–792. P, Szegedi A (2013). What does the HAMD mean? Journal
Fava GA, Rafanelli C, Grandi S, Conti S, Belluardo P (1999). of Affective Disorders 148(2), 243–248.
The role of residual subthreshold depressive symptoms in Maier W, Gänsicke M, Weiffenbach O (1997). The relationship
early episode relapse in unipolar major depressive disorder between major and subthreshold variants of unipolar
– reply. A.M.A. Archives of General Psychiatry 56(8), 764–765. depression. Journal of Affective Disorders 45(1), 41–51.
Flint AJ, Rifat SL (1997). The effect of treatment on the Maj M, Veltro F, Pirozzi R, Lobrace S, Magliano L (1992).
two-year course of late-life depression. The British Journal of Pattern of recurrence of illness after recovery from an
Psychiatry 170(3), 268–272. episode of major depression: a prospective study. The
Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori American Journal of Psychiatry 149(6), 795–800.
PW, Rush AJ, Weissman MM (1991). Conceptualization Martínez-Amorós E, Cardoner N, Soria V, Gálvez V,
and rationale for consensus definitions of terms in major Menchón JM, Urretavizcaya M (2012). Long-term
depressive disorder: remission, recovery, relapse, and treatment strategies in major depression: a 2-year
recurrence. A.M.A. Archives of General Psychiatry 48(9), 851– prospective naturalistic follow-up after successful
855. electroconvulsive therapy. The Journal of ECT 28(2), 92–97.
Hawley CJ, Gale TM, Sivakumaran T (2002). Defining Mattisson C, Bogren M, Horstmann V, Munk-Jörgensen P,
remission by cut off score on the MADRS: selecting the Nettelbladt P (2007). The long-term course of depressive
optimal value. Journal of Affective Disorders 72(2), 177–184. disorders in the Lundby study. Psychological Medicine 37(6),
Heinze G, Villamil V, Cortés J (2002). Relapse and 883–891.
recurrence of depressed patients: a retrospective study. Mittmann N, Mitter S, Borden EK, Herrmann N, Naranjo CA,
Salud Mental 25(1), 3–8. Shear NH (1997). Montgomery-Åsberg severity gradations.
Holma KM, Holma IAK, Melartin TK, Rytsälä HJ, Isometsä The American Journal of Psychiatry 154(9), 1320–1321.
ET (2008). Long-term outcome of major depressive disorder Moffitt TE, Caspi A, Taylor A, Kokaua J, Milne BJ,
in psychiatric patients is variable. The Journal of Clinical Polanczyk G, Poulton R (2010). How common are common
Psychiatry 69(2), 196–205. mental disorders? Evidence that lifetime prevalence rates
Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, are doubled by prospective versus retrospective
Coryell W, Paulus MP, Kunovac JL, Leon AC, Mueller TI, ascertainment. Psychological Medicine 40(6), 899–909.
Rice JA, Keller MB (1998). Major depressive disorder: a Moher D, Liberati A, Tetzlaff J, Altman DG,
prospective study of residual subthreshold depressive PRISMA Group (2009). Preferred reporting items for
symptoms as predictor of rapid relapse. Journal of Affective systematic reviews and meta-analyses: the PRISMA
Disorders 50(2), 97–108. statement. PLoS Medicine 6(6), e1000097.
Judd LL, Paulus MJ, Schettler PJ, Akiskal HS, Endicott J, Mueller TI, Leon AC, Keller MB, Solomon DA, Endicott J,
Leon AC, Maser JD, Mueller T, Solomon DA, Keller MB Coryell W, Warshaw M, Maser JD (1999). Recurrence after
(2000). Does incomplete recovery from first lifetime major recovery from major depressive disorder during 15 years of
depressive episode herald a chronic course of illness? The observational follow-up. The American Journal of Psychiatry
American Journal of Psychiatry 157(9), 1501–1504. 156(7), 1000–1006.
Judd LL, Schettler PJ, Rush AJ, Coryell WH, Fiedorowicz Naz B, Craig TJ, Bromet EJ, Finch SJ, Fochtmann LJ, Carlson
JG, Solomon DA (2016). A new empirical definition of GA (2007). Remission and relapse after the first hospital
major depressive episode recovery and its positive impact admission in psychotic depression: a 4-year naturalistic
on future course of illness. The Journal of Clinical Psychiatry follow-up. Psychological Medicine 37(8), 1173–1181.
77(8), 1065–1073. Nierenberg AA, Husain MM, Trivede MH, Fava M, Warden
Kanai T, Takeuchi H, Furukawa TA, Yoshimura R, D, Wisniewski SR, Miyahara S, Rush AJ (2010). Residual
Imaizumi T, Kitamura T, Takahashi K (2003). Time to symptoms after remission of major depressive disorder
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227Definitions in depression: a systematic review 561
with citalopram and risk of relapse: a STAR*D report. Bender W, Heuser I, Zeiler J, Gaebel W, Riedel M, Falkai
Psychological Medicine 40(1), 41–50. P, Möller H-J (2014). Three-Year long-term outcome of 458
O’Leary D, Costello F, Gormley N, Webb M (2000). naturalistically treated inpatients with major depressive
Remission onset and relapse in depression: an 18-month episode: severe relapse rates and risk factors. European
prospective study of course for 100 first admission patients. Archives of Psychiatry and Clinical Neuroscience 264(7),
Journal of Affective Disorders 57(1), 159–171. 567–575.
O’Leary D, Hickey T, Lagendijk M, Webb M (2010). Onset Shea MT, Elkin I, Imber SD, Sotsky SM, Watkins JT,
of remission and relapse in depression: testing operational Collins JF, Pilkonis PA, Beckham E, Glass DR, Dolan RT,
criteria through course description in a second Dublin Parloff MB (1992). Course of depressive symptoms over
cohort of first-admission participants. Journal of Affective follow-up: findings from the National Institute of Mental
Disorders 125(1), 221–226. Health Treatment of Depression Collaborative Research
Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Program. A.M.A. Archives of General Psychiatry 49(10), 782–
Barocka A (1995). Residual symptoms after partial 787.
remission: an important outcome in depression. Solomon DA, Keller MB, Leon AC, Mueller TI, Lavori PW,
Psychological Medicine 25(6), 1171–1180. Shea MT, Coryell W, Warshaw M, Turvey C, Maser JD,
Peselow ED, Tobia G, Karamians R, Pizano D, IsHak WW Endicott J (2000). Multiple recurrences of major depressive
(2015). Prophylactic efficacy of fluoxetine, escitalopram, disorder. The American Journal of Psychiatry 157(2), 229–233.
sertraline, paroxetine, and concomitant psychotherapy in Spijker J, De Graaf R, Bijl RV, Beekman ATF, Ormel J,
major depressive disorder: outcome after long-term Nolen WA (2002). Duration of major depressive episodes in
follow-up. Psychiatry Research 225(3), 680–686. the general population: results from The Netherlands
Pintor L, Torres X, Navarro V, Matrai S, Gastó C (2004). Is Mental Health Survey and Incidence Study (NEMESIS). The
the type of remission after a major depressive episode an British Journal of Psychiatry 181(3), 208–213.
important risk factor to relapses in a 4-year follow up?. Taylor WD, McQuoid DR, Steffens DC, Krishnan KRR
Journal of Affective Disorders 82(2), 291–296. (2004). Is there a definition of remission in late-life
Prien RF, Carpenter LL, Kupfer DJ (1991). The definition and depression that predicts later relapse?
operational criteria for treatment outcome of major Neuropsychopharmacology 29(12), 2272–2277.
depressive disorder: a review of the current research Van Londen L, Molenaar RPG, Goekoop JG, Zwinderman
literature. A.M.A. Archives of General Psychiatry 48(9), 796– AH, Rooijmans HGM (1998). Three- to 5-year prospective
800. follow-up of outcome in major depression. Psychological
Riedel M, Möller H-J, Obermeier M, Schennach-Wolff R, Medicine 28(3), 731–735.
Bauer M, Adli M, Kronmüller K, Nickel T, Brieger P, Van Weel-Baumgarten E, Van den Bosch W, Van den
Laux G, Bender W, Heuser I, Zeiler J, Gaebel W, Hoogen H, Zitman FG (1998). Ten year follow-up of
Seemüller F (2010). Response and remission criteria in depression after diagnosis in general practice. The British
major depression – A validation of current practice. Journal Journal of General Practice 48(435), 1643–1646.
of Psychiatric Research 44(15), 1063–1068. Wakefield JC, Schmitz MF (2013). When does depression
Riso LP, Thase ME, Howland RH, Friedman ES, Simons become a disorder? Using recurrence rates to evaluate the
AD, Tu XM (1997). A prospective test of criteria for validity of proposed changes in major depression
response, remission, relapse, recovery, and recurrence in diagnostic thresholds. World Psychiatry 12(1), 44–52.
depressed patients treated with cognitive behavior therapy. Whiteford HA, Harris MG, McKeon G, Baxter A, Pennell C,
Journal of Affective Disorders 43(2), 131–142. Barendregt JJ, Wang J (2013). Estimating remission from
Romera I, Pérez V, Menchón JM, Polavieja P, Gilaberte I untreated major depression: a systematic review and
(2011). Optimal cutoff point of the Hamilton rating scale for meta-analysis. Psychological Medicine 43(8), 1569–1585.
depression according to normal levels of social and World Health Organization (1993). The ICD-10 Classification
occupational functioning. Psychiatry Research 186(1), 133– of Mental and Behavioural Disorders: Diagnostic Criteria for
137. Research. World Health Organization: Geneva.
Rush AJ, Kraemer HC, Sackeim HA, Fava M, Trivedi MH, World Health Organization (2017) Depression fact sheet.
Frank E, Ninan PT, Thase ME, Gelenberg AJ, Kupfer DJ, (http://www.who.int/mediacentre/factsheets/fs369/en/).
Regier DA, Rosenbaum JF, Ray O, Schatzberg AF (2006). Accessed 1 October 2017.
Report by the ACNP task force on response and remission Yiend J, Paykel E, Merritt R, Lester K, Doll H, Burns T
in major depressive disorder. Neuropsychopharmacology 31 (2009). Long term outcome of primary care depression.
(9), 1841–1853. Journal of Affective Disorders 118(1), 79–86.
Sacchetti E, Frank E, Siracusano A, Racagni G, Vita A, Zimmerman M, Chelminski I, Posternak M (2004a). A
Turrina C (2015). Functional impairment in patients with review of studies of the Montgomery-Asberg Depression
major depression in clinical remission: results from the Rating Scale in controls: implications for the definition of
VIVAL-D-Rem, a nationwide, naturalistic, cross-sectional remission in treatment studies of depression. International
survey. International Clinical Psychopharmacology 30(3), 129– Clinical Psychopharmacology 19(1), 1–7.
141. Zimmerman M, Chelminski I, Posternak M (2004b). A
Seemüller F, Meier S, Obermeier M, Musil R, Bauer M, review of studies of the Hamilton Depression Rating Scale
Adli M, Kronmüller K, Holsboer F, Brieger P, Laux G, in healthy controls: implications for the definition of
Downloaded from https://www.cambridge.org/core. IP address: 46.4.80.155, on 28 Oct 2021 at 14:26:20, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms.
https://doi.org/10.1017/S2045796018000227You can also read
